Leveraging Interacting Signaling Pathways to Robustly Improve the Quality and Yield of Human Pluripotent Stem Cell-derived Hepatoblasts and Hepatocytes

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2022 Feb 5

PMID 35120625

Authors

Claudia Raggi

Marie-Agnes MCallum

Quang Toan Pham

Perrine Gaub

Silvia Selleri

Nissan Vida Baratang

Chenicka Lyn Mangahas

Gael Cagnone

Bruno Reversade

Jean-Sebastien Joyal

Massimiliano Paganelli

Affiliations

Soon will be listed here.

Abstract

Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs) have shown great potential as an alternative to primary human hepatocytes (PHHs) for in vitro modeling. Several differentiation protocols have been described to direct PSCs toward the hepatic fate. Here, by leveraging recent knowledge of the signaling pathways involved in liver development, we describe a robust, scalable protocol that allowed us to consistently generate high-quality bipotent human hepatoblasts and HLCs from both embryonic stem cells and induced PSC (iPSCs). Although not yet fully mature, such HLCs were more similar to adult PHHs than were cells obtained with previously described protocols, showing good potential as a physiologically representative alternative to PHHs for in vitro modeling. PSC-derived hepatoblasts effectively generated with this protocol could differentiate into mature hepatocytes and cholangiocytes within syngeneic liver organoids, thus opening the way for representative human 3D in vitro modeling of liver development and pathophysiology.

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